The role of the T1 neuronal circuit in pheromone behaviors Research Summary Understanding the molecular and cellular basis of behavior is of great importance, both for the academic interest of understanding the substrates underlying behavior, and for the potential clinical relevance of understanding human behavior and mental illness. We propose to study a simple behavior paradigm in a genetically tractable animal model system;volatile pheromone-triggered behaviors in Drosophila melanogaster. 11-cis- vaccenyl acetate (cVA) is a male-produced pheromone that mediates aggregation and sexual behavior in Drosophila. cVA detection occurs through a small number of olfactory neurons located in trichoid sensilla on the antenna. Neurons within a subset of trichoid sensilla (the T1 sensilla) are exquisitely tuned to cVA and appear to be the primary cVA perception pathway. However, recent work also implicates a distinct set of trichoid neurons expressing Or65a in cVA-mediated behavior and learning. To begin to dissect the contribution of these two pathways in cVA-induced behavior, we will examine the effect of the loss or the constitutive activation of the T1 pathway on behavior. We propose two specific aims. First, we will create flies expressing a dominant, activating variant of the extracellular pheromone-binding protein LUSH that will allow us to manipulate the activity in this neuronal circuit. Second, we will use flies expressing activated LUSH or mutants with reduced T1 activity to dissect the role of increased or decreased activity in the T1 circuit on behavior. The results of these studies will provide new insights into the role of the T1 neuronal circuit in cVA-induced behavior. PUBLIC HEALTH RELEVANCE Pheromones trigger social behaviors in animals that are genetically hard wired, such as reproduction and aggression. In insects, pheromones guide mating behavior and aggregation to food sources. Therefore, understanding how pheromones are perceived and decoded by the insect nervous system could be of great practical benefit to control insects that transmit diseases or destroy agriculture. We study pheromone signaling in the Drosophila, where we can apply genetic analysis to behavior. The pheromone cVA is important for mating and aggregation in fruit flies, and appears to be sensed through two different neuronal circuits. Here, we will use genetic manipulations to activate or inactivate these pathways to elucidate the behavioral contributions of each to mating and aggregation behaviors. The expected results from these studies will help us understand how pheromone perception occurs in insects in general.